Valproic acid is currently marketed in the United States as an anticonvulsant, medicament. It is available in the form of a soft gelatin capsule dosage form, and may also be obtained as a syrup containing the sodium salt of valproic acid, i.e., sodium valproate.
The administration of valproic acid has been reported to cause gastro-intestinal side effects including anorexia, nausea and vomiting. Abdominal cramps, diarrhea and constipation have also been observed. Valproic acid is also known to have an irritating effect upon the mucosa of the mouth and throat. The latter effect is such that patients being administered the soft gelatin capsule dosage form are warned as follows: The capsules should be swallowed without chewing to avoid local irritation of the mouth and throat (see Physicians Desk Reference, page 512, 34th ed; 1980, Medical Economics Company, Oradell, N.J. 07649). This untoward characteristic is an obvious disadvantage to the administration of the soft gelatin capsule dosage form. This characteristic is a particular problem when the dosage form is intended to be administered to pediatric and geriatric patients; since many of these classes of patients are either incapable of understanding the precautionary instructions or are not able to swallow the capsule. The syrup dosage form (sodium valproate) has the attendant problems of being, (1) inconvenient to use since the proper volume to deliver the necessary dose must be individually measured for each administration; and (2) being non-portable since a container of liquid as well as a measuring device must be transported. These problems are particularly troublesome for self administration by a pediatric or geriatric patient.
It should also be noted that since sodium valproate is a hygroscopic material, the production of a compacted dosage form (tablet) containing this substance is precluded.
It is therefore clear that it would be desirable to provide an improved oral dosage form for the administration of this medicament.